The development and validation of a turbulent flow-liquid chromatography-tandem mass spectrometric method for the simultaneous quantification of citalopram, sertraline, bupropion and hydroxybupropion in serum.

OBJECTIVES: Depression is a rapidly growing issue in the United States. There are many drug classes that may be used to treat depression, including the selective serotonin-reuptake inhibitors (SSRIs) citalopram (Celexa®) and sertraline (Zoloft®), as well as the aminoketone bupropion (Wellbutrin®). However, therapeutic efficacy and treatment success is often variable, requiring changes in dosing regimens or drug selection. Methods for drug quantification can become important tools in the assessment of drug efficacy to optimize treatment regimens. Here, we present a turbulent flow-liquid chromatography-tandem mass spectrometric (TFC-MS/MS) method for the robust, simultaneous quantification of citalopram, sertraline, bupropion and its active metabolite, hydroxybupropion (OH-bupropion).

DESIGN AND METHODS: Serum spiked with the aforementioned antidepressants, along with their corresponding isotopically labeled internal standards was subjected to protein precipitation. Samples were injected onto a TFC column for on-line solid phase extraction and a Hypersil Gold C18 column for chromatographic separation. Detection was achieved using a TSQ Vantage mass spectrometer. Assay validation followed FDA bioanalytical guidelines.

RESULTS: The analytical measuring range for all analytes spanned from 5 to 1000ng/mL. Intra- and inter-assay precision across four quality control levels were ≤9.2% and ≤14.8%, respectively. A comparison to other LC-MS/MS methods resulted in a strong correlation with correlation coefficients ranging from 0.9929 to 0.9971. Carryover, stability, recovery, matrix effects, extraction and processing efficiency were also deemed acceptable in accordance with FDA recommendations.

CONCLUSIONS: The development and validation of this TFC-MS/MS method allow for the robust and high-throughput quantification of commonly prescribed antidepressants.